title: Functional salivary gland regeneration by transplantation of a bioengineered organ germ.
abstract: Salivary gland hypofunction, also known as xerostomia, occurs as a result of radiation therapy for head cancer, Sjögren's syndrome or aging, and can cause a variety of critical oral health issues, including dental decay, bacterial infection, mastication dysfunction, swallowing dysfunction and reduced quality of life. Here we demonstrate the full functional regeneration of a salivary gland that reproduces the morphogenesis induced by reciprocal epithelial and mesenchymal interactions through the orthotopic transplantation of a bioengineered salivary gland germ as a regenerative organ replacement therapy. The bioengineered germ develops into a mature gland through acinar formations with a myoepithelium and innervation. The bioengineered submandibular gland produces saliva in response to the administration of pilocarpine and gustatory stimulation by citrate, protects against oral bacterial infection and restores normal swallowing in a salivary gland-defective mouse model. This study thus provides a proof-of-concept for bioengineered salivary gland regeneration as a potential treatment of xerostomia.
authors.affiliation: 1] Research Institute for Science and Technology, Tokyo University of Science, Noda 278-8510, Japan [2] Division of Research and Development, Organ Technologies Inc, Tokyo 01-0048, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Ogawa
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Oshima
authors.forename: Aya
authors.initials: A
authors.lastname: Imamura
authors.forename: Yurie
authors.initials: Y
authors.lastname: Sekine
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ishida
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yamashita
authors.forename: Kei
authors.initials: K
authors.lastname: Nakajima
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Hirayama
authors.forename: Tetsuhiko
authors.initials: T
authors.lastname: Tachikawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Tsuji
mesh_terms: D000818:Animals; D019343:Citric Acid / Q000494:pharmacology; D004622:Embryo, Mammalian; D053595:Embryonic Stem Cells / Q000166:cytology*; D004847:Epithelial Cells / Q000473:pathology; D006085:Graft Survival / Q000502:physiology; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010862:Pilocarpine / Q000494:pharmacology; D020127:Recovery of Function; D012038:Regeneration; D033581:Stem Cell Transplantation; D013363:Submandibular Gland / Q000294:innervation / Q000473:pathology / Q000601:surgery*; D023822:Tissue Engineering; D014184:Transplantation, Homologous; D014987:Xerostomia / Q000473:pathology / Q000601:surgery / Q000628:therapy*
chemical_list: D010862:Pilocarpine; D019343:Citric Acid